Multiple-biosensor article

ABSTRACT

An article suitable for conducting one or more assays with an apparatus, e.g., a meter, for determining the presence or concentration of an analyte in a sample of biological fluid. The article contains a plurality of biosensors arranged in such a manner that each of the biosensors can be utilized before the article must be removed from the apparatus.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to biosensors, and in particular, articlescontaining a plurality of biosensors suitable for use with an apparatus,e.g., an analyte meter, for determining the presence or concentration ofanalytes in a biological sample.

2. Discussion of the Art

The prevalence of diabetes has been increasing markedly in the world. Atthis time, diagnosed diabetics represent about 3% of the population ofthe United States. It is believed that the total actual number ofdiabetics in the United States is over 16,000,000. Diabetes can lead tonumerous complications, such as, for example, retinopathy, nephropathy,and neuropathy.

The most important factor for reducing diabetes-associated complicationsis the maintenance of an appropriate level of glucose in the bloodstream. The maintenance of the appropriate level of glucose in the bloodstream may prevent and even reverse many of the effects of diabetes.

Glucose monitoring devices of the prior art have operated on theprinciple of taking blood from an individual by a variety of methods,such as by needle or lancet. The individual then coats a paper stripcarrying chemistry with the blood, and finally inserts the blood-coatedstrip into a blood glucose meter for measurement of glucoseconcentration by determination of change in reflectance.

The medical apparatus of the prior art for monitoring the level ofglucose in the blood stream required that an individual have separatelyavailable a needle or lancet for collecting blood from the individual,strips carrying blood chemistry for creating a chemical reaction withrespect to the glucose in the blood stream and changing color, and ablood glucose meter for reading the change in color indicating the levelof glucose in the blood stream. The level of blood glucose, whenmeasured by a glucose meter, is read from a strip carrying the bloodchemistry through the well-known process of reading reflectometers forglucose oxidation.

The prior art discloses numerous electrochemical and optical biosensors,e.g., test strips, for measuring the concentration of an analyte in atest sample. In particular, the art discloses disposable test strips forthe measurement of glucose level in whole blood that deal primarily withthe reaction layer used to generate an analytical response, the mode ofmeasurement, and the algorithms used in the measurement.

Electrochemical assays for determining the concentrations of enzymes ortheir substrates in complex mixtures of liquids have been developed.Test strips (i.e., biosensors in the form of test strips) are useful inexternal testing. In external testing, test strips can function in anon-invasive manner (i.e., as strips that come into contact with bloodwithdrawn by a syringe or a lancing device). In particular, test stripsfor biomedical applications (e.g., whole blood analyses) have beendeveloped for the determination of glucose levels in biological samples.In general, test strips comprise electrochemical cells in which therecan be working electrodes, counter electrodes, and reference electrodes.The potential of the working electrode is maintained at a constant valuerelative to that of the reference electrode.

A minimally painful technique for obtaining body fluids is described inU.S. Pat. No. 6,063,039. This patent discloses an apparatus forobtaining blood for diagnostic tests. The apparatus comprises a housinghaving a sealable chamber located therein and a sealable opening influid communication with the sealable chamber, a power source, a vacuumpump operably connected to the power source, the vacuum pump incommunication with the sealable chamber, a lancing assembly positionedwithin the sealable chamber, and a fluid collector (biosensor in theform of a test strip) positioned in the sealable chamber, the fluidcollector in fluid communication with the sealable opening. However,only one fluid collector can be positioned in the housing of theapparatus at a time. The user must manually remove a consumed fluidcollector from the housing, before another fluid collector can beinserted therein. It would be desirable to improve that system in orderto allow more than one fluid collector to be inserted into the housingat a time, in order to simplify the use of the apparatus for the user.

Osaka et al., U.S. Pat. No. 5,228,972, discloses an apparatus formeasuring concentration of test substances in liquid. The apparatuscomprises one or more thin plates having one or more openings throughwhich a test substance to be measured is penetrated, in a predeterminedposition thereof, diffusion-limiting membranes for limiting diffusion ofthe test substance adhered to the thin plates for covering the openings,a casing for housing the one or more thin plates, and a drivingmechanism for moving the thin plate by a predetermined distance. Thethin plate may be disk-shaped, strip-shaped, or elongated. The elongatedthin plate may further be rolled. The casing is provided with thedriving mechanism and is positioned in a test apparatus body having aconcentration-measuring electrode therein. Multiple measurements ofconcentration of a test substance are carried out by moving the thinplate by the driving mechanism to position the diffusion-limitingmembrane having the test solution deposited thereon to the positionavailable to contact with the concentration measuring electrode, whilekeeping the casing placed in the test apparatus body. However, U.S. Pat.No. 5,228,972 requires a casing and a diffusion-limiting membrane.Moreover, the thin plate must be moved by the driving mechanism toposition the diffusion-limiting membrane having the test solutiondeposited thereon to a position available to contact theconcentration-measuring electrode, while keeping the casing placed inthe test apparatus body.

Nozoe et al., U.S. Pat. No. 5,741,634, discloses a disk-shaped sensorbody containing a plurality of elemental sensors radially extendedoutward from the circumference thereof. The sensor body is made from aninsulating material. The circumferential portion of the sensor body isshaped to have v-shaped notches equidistantly and angularly arrayedtherearound. Of these notches, the adjacent notches define a trapezoidalpart. The notches and trapezoidal parts are alternately arrayed on thecircumference of the sensor body. The sensor elements are formed in thetrapezoidal parts. In the sensor circuit, a sensor portion is formed ofa counter electrode, a reference electrode, a first working electrode,and a second working electrode. Additional films are positioned over thetwo working electrodes. However, U.S. Pat. No. 5,741,634 does notprovide a means for integrating the measurement function with the sampleextraction function and sample transfer function.

The foregoing patents describe several ways to package a plurality oftest strips for determining the concentration of analytes. However,neither of these patents disclose a device wherein a device forcollection of biological samples and storage of a plurality ofbiosensors are integrated into a single entity. “Ascensia Breeze” teststrips (Bayer) and “Accu-Chek Compact” test strips (Roche) involvepackaging a plurality of individual test strips in sealed chambers andindexing unused test strips into position for measuring theconcentration of glucose. However, these test strips require complicatedadvancing and indexing mechanisms to pierce sealed chambers, to advanceand index the test strips into position for testing, and to eject usedtest strips after testing.

SUMMARY OF THE INVENTION

This invention provides an article suitable for conducting one or moreassays with an apparatus, e.g., a meter, for determining the presence orconcentration of an analyte in a sample of biological fluid. The articlecontains a plurality of biosensors arranged in such a manner that eachof the biosensors can be utilized before the article must be removedfrom the apparatus.

In one embodiment, the article comprises a thin, flat plate, preferablyin the shape of a disk. The thin, flat plate has a plurality of sectors.Each of the sectors has a biosensor applied thereto. Attached to thethin, flat plate is a backing, preferably having substantially the sameperipheral dimensions as does the plate. The backing also has aplurality of sectors. The backing can be constructed to facilitate theuse of a device for forming an opening in the skin of a subject. In thisembodiment, each of the sectors of the backing has a recessed portionfor allowing a lancing device to pass therethrough. Each sector in thethin, flat plate has an aperture and each recessed portion in eachsector in the backing has an aperture, each of the apertures in thethin, flat plate being in register with an aperture in one of therecessed portions in the backing.

The multiple-biosensor article can be loaded into an analyte meter byinserting the article into a slot located on or in the analyte meter orby opening a door or cover on or in the analyte meter and inserting thearticle into the area provided. Once loaded in the analyte meter, themultiple-biosensor article can be advanced or indexed or both by eitherrotating or translating the article automatically, semi-automatically,or manually. Advancing or indexing or both can be carried out by suchmechanisms as motor(s), gear(s), pulley(s), belt(s), solenoid(s),nano-muscle(s), and the like. A lancing blade can pass through theapertures in the plate and the backing on the way to lancing the skin.

After the lancing step, the multiple-biosensor article can be indexedslightly to cover the lancing site with the sample pick-up area of abiosensor to fill the reaction site of the biosensor. After a test iscompleted, the article may be advanced or indexed by rotation,automatically, semi-automatically, or manually, toward a storage areawithin the analyte meter.

In a second embodiment, the thin, flat plate can be deleted, and thebacking can be constructed so as to perform the functions of both thebacking and the thin, flat plate of the first embodiment.

In a third embodiment, the biosensors can be manufactured and stored inthe form of a roll. The roll comprises a plurality of segments arrangedlinearly. Each segment contains a biosensor. At least a portion of eachsegment has an opening therein to allow a lancing device to penetratethe skin without striking the solid portions of the segment. In thisembodiment, the segments can be separated by score lines to enableremoval and disposal of a used biosensor.

In a fourth and a fifth embodiment, both of which can be in the form ofa roll, each segment is attached to an adjacent segment by a hinge. Inthe fourth embodiment, the hinge is formed of a flexible, tearablematerial, which can be torn by the hand to detach a given biosensor fromthe adjacent biosensor. In the fifth embodiment the hinge comprises apin and a holder for the pin, whereby a given biosensor can be detachedfrom the adjacent biosensor by separating the pin from the holder.

In a sixth embodiment, a single-use lancet can be provided for eachbiosensor. This embodiment eliminates the need to provide a lancingdevice having complex cocking and triggering mechanisms.

The invention provides an integrated system comprising an analyte meterand biosensors, wherein the measurement of the concentration of theanalyte need not require the intervention of the user for loadingbiosensors into the analyte meter until the all the biosensors on thearticle, e.g., the disk or roll, whichever the case may be, areconsumed. In those embodiments where a lancet is provided for eachbiosensor, the user can perform a multiplicity of tests before manualinsertion of lancets is required. In those embodiments where sampleextraction and retention of used biosensors in the analyte meter areintegrated, contamination by biohazards can be reduced.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of one embodiment of the article of thisinvention.

FIG. 2 is an exploded perspective view of the article of FIG. 1, whereinthe backing of the article is shown above the plate of the article, andan optional shield is shown above the backing. An optional layer ofadhesive is shown between the plate and the backing.

FIG. 3 is an exploded perspective view of the article of FIG. 1, whereinthe wherein the plate of the article is shown above the backing of thearticle. An optional layer of adhesive is shown between the plate andthe backing.

FIG. 4 is a perspective view of the article of this invention showinghow the article of FIG. 1 is placed in an analyte meter.

FIG. 5 is a perspective view of the article of this invention showingthe article of FIG. 1 after being placed in an analyte meter.

FIG. 6 is a perspective view of another embodiment of the article ofthis invention.

FIG. 7 is an exploded perspective view of the article of FIG. 6, whereinthe positioning of the biosensors relative to the recesses is shown.

FIG. 8 is a perspective view, greatly enlarged, of the surface of arecess of the article of FIG. 7.

FIG. 9 is a perspective view of another embodiment of the article ofthis invention. In this figure, the article is shown as being unrolled.Also, in this figure, one major surface of each biosensor in the articleis visible.

FIG. 10 is a perspective view of the embodiment of the article of FIG.9. In this figure, the article is shown as being unrolled. Also, in thisfigure, a major surface of each biosensor in the article, the surfacebearing the electrode arrangement, is not visible.

FIG. 11 is an exploded perspective view, greatly enlarged, of thearticle of FIG. 9, wherein the positioning of the biosensors relative tothe recesses is shown. The major surface of the biosensor bearing theelectrode arrangement is not shown.

FIG. 12 is a perspective view of another embodiment of the article ofthis invention. In this figure, the article is shown as being unrolled.Also, in this figure, one major surface of each biosensor in the articleis visible.

FIG. 13 is an exploded perspective view of the article of FIG. 12. Inthis figure, the article is shown as being unrolled. Also, in thisfigure, a major surface of each biosensor in the article, the surfacebearing the electrode arrangement, is not visible.

FIG. 14 is a perspective view, greatly enlarged, of an individual recessof the article of FIG. 12 and of FIG. 13.

FIG. 15 is a perspective view of another embodiment of the article ofthis invention. In this figure, the article is shown as being unrolled.Also, in this figure, one major surface of each biosensor in the articleis visible.

FIG. 16 is an exploded perspective view of the article of FIG. 15. Also,in this figure, a major surface of each biosensor in the article, thesurface bearing the electrode arrangement, is not visible.

FIG. 17 is a perspective view, greatly enlarged, of an individual recessof the article of FIG. 15 and of FIG. 16.

FIG. 18 is a second perspective view of the article of FIG. 15. In thisfigure, the article is shown as being unrolled. Also, in this figure,only a minor surface of each biosensor is visible.

FIG. 19 is an exploded perspective view of another embodiment of thearticle of this invention, wherein a plurality of single-use lancetattachments is utilized. The article is similar to the article shown inFIGS. 1-3.

FIG. 20 is an exploded perspective view of a percussion device that canbe adapted to activate the lancet attachments shown in FIG. 19.

FIG. 21 is a perspective view of a biosensor suitable for use in thearticles of FIGS. 6-18.

FIG. 22 is a side view in elevation of the biosensor of FIG. 21.

DETAILED DESCRIPTION

As used herein, the term “biosensor” means an element of the article ofthis invention that provides qualitative or quantitative informationrelating to an analyte in a biological sample. A biosensor contains abiological component such as enzyme, antibody, etc., to impartselectivity to the analyte of interest in a complex sample, such asbiological fluid, e.g., blood, interstitial fluid.

As used herein, the expression “test strip” means a biosensor in theform of a strip that contains the necessary components to generate ameasurable signal when exposed to a liquid sample. Test strips aretypically single-use, disposable articles. In general, a test stripcomprises a backing having an electrode arrangement thereon.

As used herein, the term “sector” means a region of the article of theinvention that contains a single electrode arrangement and a set ofapertures for positioning a biosensor at a sample receiving site andtransferring the received sample from the sample receiving site to areaction site. In certain embodiments of this invention, the articlecomprises a plurality of sectors arranged such that each sector isadjacent to two neighboring sectors.

As used herein, the term “sector” means a part in which the entirety ofthe article can be divided. A sector contains a single electrodearrangement and a set of apertures for positioning a biosensor at asample receiving site and transferring the received sample from thesample receiving site to a reaction site. In certain embodiments of thisinvention, the article comprises a plurality of sectors arranged suchthat each sector is adjacent to two neighboring sectors

As used herein, the term “segment” also means a part in which theentirety of the article can be divided. A segment contains a singleelectrode arrangement and a set of apertures for positioning a biosensorat a sample receiving site and transferring the received sample from thesample receiving site to a reaction site. In certain embodiments of thisinvention, the article comprises a plurality of segments arranged suchthat each segment is adjacent to two neighboring segments. In general,the term “sector” is used to describe circular embodiments, and the term“segment” is used to describe linear embodiments.

As used herein, the expression “electrode arrangement” means the mannerin which electrodes are arranged to form a biosensor. Typically, theelectrode arrangement of a biosensor comprises a working electrode, areference electrode, and a counter electrode (or in place of thereference electrode and counter electrode an electrode that functions asboth reference electrode and counter electrode). Reagents that arerequired for generating a measurable signal upon electrochemicalreaction with an analyte in a sample to be assayed are placed over theelectrodes so that the reagents cover at least one of the electrodes. Insome cases, the reagents and an inert electrode (such as carbon,palladium, gold) serve as the working electrode and the dual-purposereference/counter electrode. In these situations, the reagents arerequired to be on both electrodes.

Referring now to FIGS. 1-3, which illustrate one embodiment of thisinvention, the article 10 comprises a thin, flat plate 12 and a backing14. The thin, flat plate 12 is in the form of a disk and has a pluralityof sectors 16, each of which contains a biosensor 18 on a major surface12 a thereof. Each biosensor 18 comprises an electrode arrangement,which will be described later. The thin, flat plate 12 further comprisesa plurality of apertures 20, each aperture 20 being adjacent to anelectrode arrangement of a given biosensor 18. Each of the apertures 20is shown as being circular in shape, although other shapes, e.g.,elliptical, triangular, rectangular, are suitable for the invention. Thepurpose of the aperture 20 is to provide an opening through which alancing element may pass in order to form an opening in the skin of asubject or patient. Each aperture 20 further has a notch 22 formed atthe boundary thereof. The purpose of the notch 22 is to provide an areaat which a biological sample from the subject or patient can easily bedrawn into the biosensor 18. The notch 22 breaks the surface tension ofthe liquid and provides a larger surface area for application of aliquid sample.

The thin, flat plate 12 may further comprise a plurality of relativelysmall apertures 24, each relatively small aperture 24 being adjacent toa given electrode arrangement. The purpose of the small apertures 24 isto receive a pin or other type of fastener to properly align the backing14 with the thin, flat plate 12. In the embodiment shown in FIGS. 1-3,the thin, flat plate 12 has a relatively large aperture 26 in the centerthereof. The purpose of the relatively large aperture 26 is to allow adrive assembly to be positioned to engage the article 10 of thisinvention.

The backing 14 is substantially congruent with the thin, flat plate 12.The backing 14 has a thickness greater than the thickness of the thin,flat plate 12. In the embodiment shown in FIG. 1, the backing 14 has arelatively large aperture 28 in the center thereof. The purpose of therelatively large aperture 28 is to allow a drive assembly to bepositioned to engage the article 10 of this invention.

In addition, the backing 14 has a plurality of sectors 30, each sector30 corresponding to a sector 16 of the thin, flat plate 12. Each sector30 has a recessed portion 32 having a wall portion 34 and a base portion36, the base portion 36 preferably being circular in shape. In the baseportion 36 of each sector 30 is an aperture 38. When the thin, flatplate 12 and the backing 14 are properly assembled, each aperture 38 isin register with an aperture 20 of the thin, flat plate 12.

In the embodiment shown in FIGS. 1-3, the backing 14 has fifteen (15)sectors 30, each having a recessed portion 32. The purpose of therecessed portion 32 is to provide a guiding path for a lancing device(not shown) to travel in order to reach the skin of the user of thearticle of this invention. The area of the recessed portion 32 (i.e.,the area of the base portion 36) must be sufficiently great to allowpassage of the lancing device. The depth of the recessed portion (i.e.,the length of the wall portion 34) must be sufficiently great to allowthe lancet to be guided to its target but not so great as to obstruct orotherwise hinder the movement of the lancet.

In addition, in the embodiment shown in FIGS. 1-3, there are fifteen(15) apertures 20 in the thin, flat plate 12 and fifteen (15) apertures38 in the backing 14, each sector 30 in the backing 14 having oneaperture 38 and each sector 16 in the thin, flat plate 12 having oneaperture 20. The apertures 38 in the backing 14 and the apertures 20 inthe thin, flat plate 12 are aligned, whereby a lancing device passesthrough both apertures 20 and 38 to form an opening in the skin, andbiological fluid, typically blood, begins its flow to a biosensor 18from the aperture 20. The particular size of the apertures 20 and 38 isnot critical, but if they are too large, the number of biosensors 18that can be disposed on a thin, flat plate 12 will be reduced, and ifthey are too small the rate of flow of biological fluid will be too low.The size of the apertures 20 and 38 can be selected to (a) optimize thenumber of biosensors 18 that can be retained on the thin, flat plate 12and (b) the rate of flow of the biological fluid.

In the embodiment shown in FIGS. 1-3, the major surfaces of the thin,flat plate 12 are circular in shape to facilitate advancement of thebiosensors 18 in an apparatus, i.e., meter, i.e., an analyte meter.While possibly not as effective as a circular shape, other shapes, e.g.,elliptical, triangular, rectangular, can be employed. The dimensions ofthe thin, flat plate 12 are not critical. However, it is desired thatthe thin, flat plate 12 at least have sufficient surface area to carry asingle day's supply of biosensors 18, typically three to four biosensors18. As biosensors 18 are reduced in size, it is expected that as many astwenty-five to thirty-five biosensors 18 can be carried on the thin,flat plate 12. The thickness of the thin, flat plate 12 is not critical,but it should be sufficiently thick to ensure structural integrity.Typical dimensions of the thin, flat plate 12 can range from about 1 cmto about 10 cm in diameter and from about 0.5 mm to about 5 mm inthickness.

Because the thin, flat plate is expected to be disposable, it ispreferred that the thin, flat plate 12 be constructed of a relativelyinexpensive material, such as, for example, sheet metal, rigid,semi-rigid, or flexible polymeric materials, paper, e.g., card stock.Examples of materials suitable for use in making the thin, flat plate 12include, but are not limited to, polyvinyl chloride, polyester,polycarbonate, and polyethylene terephthalate.

The backing 14 can be cylindrical in shape to facilitate advancement ofthe biosensors 18 in the apparatus, i.e., an analyte meter. The surfaceof the backing 14 is preferably of a shape that is substantially similarto that of the thin, flat plate 12, that is, if the major surfaces ofthe thin, flat plate 12, for example, are elliptical, triangular, orrectangular, it is preferred that the major surfaces of the backing 14also be elliptical, triangular, or rectangular, respectively. The areaof the surface of the backing 14 is preferably substantially equal tothat of the thin flat plate 12. The overall depth of the backing 14 isnot critical, but should be of sufficient length to ensure structuralintegrity. The depth must not be so great as to require the apparatusinto which it is inserted to be excessively large. Typical dimensions ofthe backing 14 can range from about 1 cm to about 10 cm in diameter andfrom about 0.5 to about 5 mm in thickness. The backing 14, like thethin, flat plate 12, is preferably made of an inexpensive material,because it too is intended to be disposable. Preferred materials forconstructing the backing 14 include polymeric materials, paper, othercellulosic materials. Because the backing 14 includes flat surfaces,recesses, and apertures, it is preferred that it be made of a polymericmaterial, whereby it can be formed by means of a molding process forforming shaped articles. Examples of materials suitable for use inmaking the backing 14 include, but are not limited to, polyester,polyethylene terephthalate, and polycarbonate. In general, the backingcan be made of any material that can be easily shaped to athree-dimensional component to support the biosensors. Paper and foilcan be used, but are not easily shaped into a three-dimensional articlehaving a substantial depth.

The major surface of the backing 14 that faces the thin, flat plate 12has a plurality of channels 40 formed therein to allow for the flow of aliquid sample. As shown in FIG. 3, one end 42 of the channel 40 is inregister with the aperture 20 to enable ease of transfer of biologicalfluid to the channel 40. The other end 44 of the channel 40 terminatesat a vent opening or at the physical end of the channel 40 or, if used,at a flow terminating interface. The portion of the channel 40 betweenthe two ends 42 and 44 can include a surfactant-coated mesh to aid thewicking of the sample into the reaction site. In other embodiments, thedimensions of the channel can be selected to allow the sample to betaken into the reaction site by capillary attraction. The article ofthis invention has flow channels to direct flow and allow reduction ofthe volume of sample. Flow channels having the appropriate dimensionscould eliminate the use of a layer of mesh. Alternatively, a layer ofmesh could be laminated onto the backing, thereby reducing the costlystep of applying the mesh to the electrode arrangement.

Each sector 30 of the article 10 has a channel 40. At the end 42 of thechannel 40 is a reaction site 46. The volume of the channel 40 isselected to contain the amount of sample needed to perform a test, e.g.,an assay to determine the concentration of glucose in blood. Theselection of the volume is based on spacing of the electrodes of theelectrode arrangement. The dimensions of the channel 40 are derived fromthe volume of liquid sample required. A typical volume for the channel40 ranges from about 0.1 microliter to about 4 microliters, therebycalling for dimension of from about 0.5 mm×0.2 mm×0.1 mm to about 2 mm×1mm×0.2 mm for a rectangularly-shaped channel.

The backing 14 can provide several functions for enhancing the use of alancing device, such as, for example, a motion-terminating element (notshown) for a mechanical lancing device or a support 48 for alight-generating device, e.g., a laser, to prevent contamination oflaser optics. The support 48 can be designated an optical shield. FIG. 2shows an optical shield 48 for the prevention of contamination of alaser. The optical shield is not required, but may be a desirableoption.

A layer of adhesive 50 can be used to adhere the backing 14 to the thin,flat plate 12. The layer of adhesive 50 is preferably placed between themajor surface of the thin, flat plate 12 that faces the major surface ofthe backing 14. The purpose of the layer of adhesive 50 is to maintainthe thin, flat plate 12 and the backing 14 in proper registration. Thelayer of adhesive 50 has small apertures 52 for alignment with the smallapertures 24 of the thin, flat plate 12. The layer of adhesive 50 has aplurality of channels 54. One end 56 of each channel 54 has an aperture58 that is in register with the apertures 20 and 38 in the thin, flatplate 12 and the backing 14, respectively. The other end 60 of thechannel is in communication with a vent opening, if necessary. While alayer of adhesive 50 can be used to bond the thin, flat plate 12 to thebacking 14, other types of fasteners can be used to bond the thin, flatplate 12 to the backing 14. Alternatives to the use of an adhesive formaintaining the backing and the thin, flat plate in proper registrationor alignment include a press-fit ring and the use of alignment posts orpins.

A second embodiment of the article of this invention is shown in FIGS.6-8. This embodiment does not utilize a thin, flat plate analogous toplate 12. Instead, this embodiment utilizes a backing that receivesbiosensors that are pre-manufactured test strips, wherein each teststrip is received into a recess in the backing. In this embodiment thearticle 110 comprises a backing 114. The backing 114 is substantially inthe form of a cylinder. In the embodiment shown in FIGS. 6-8, thebacking 114 has a relatively large aperture 126 in the center thereof.The large aperture 126 performs the same function as do the largeapertures 26 and 28 of the first embodiment (see FIGS. 1-3). Inaddition, the backing 114 has a plurality of sectors 128, each sector128 capable of retaining a test strip 130. Each sector 128 has arecessed portion 132 having a wall portion 134 and a base portion 136.As shown in FIG. 6, the base portion 136 is circular in shape. In thebase portion 136 of each sector 128 is an aperture 138. The purpose andcharacteristics of the recessed portion 132 are the same as that of therecessed portion 32 of the first embodiment (see FIGS. 1-3).

The major surface of the backing 114 opposite to the major surface ofthe backing 114 bearing the recessed portions 132 has recesses 140formed therein to allow for the placement of the test strips 130. Asshown in FIGS. 7 and 8, one end 142 of each recess 140 is adjacent to anaperture 138. The other end 144 of each recess 140 terminates at theboundary of the large aperture 126. The portion of the recess 140between the two ends 142 and 144 has dimensions whereby the recess 140is capable of accommodating a biosensor in the form of a test strip 130.Each of the apertures 138 is shown as being circular in shape, althoughother shapes, e.g., elliptical, triangular, rectangular), are suitablefor the invention. Each aperture 138 further has a notch 146 formed atthe boundary thereof. The purpose of the notch 146 is to provide an areaat which the biological sample can easily be drawn into the test strip130. The notch 146 breaks the surface tension of the liquid and providesa larger surface area for application of a liquid sample. A layer ofadhesive 148 can be used to adhere the test strip 130 to the recess 140in the backing 114.

The backing 114 can be cylindrical in shape to facilitate advancement ofthe test strips 130 in the meter, i.e., an analyte meter. The majorsurfaces of the backing 114 can be of any shape that would allowadvancement of the test strips 130 in the apparatus. Such shapesinclude, but are not limited to, circular, elliptical, triangular, orrectangular, respectively. The area of the surface of the backing 114should be sufficient to accommodate the desired number of test strips.The overall depth of the backing 114 is not critical, but should be ofsufficient length to ensure structural integrity. The depth must not beso great as to require the apparatus into which it is inserted to beexcessively large. Typical dimensions of the backing 114 can range fromabout 1 cm to about 10 cm in diameter and from about 0.5 to about 5 mmin thickness.

The backing 114 is preferably made of an inexpensive material, becauseit is intended to be disposable. Preferred materials for constructingthe backing 114 include polymeric materials, paper, other cellulosicmaterials. Because the backing 114 includes flat surfaces, recesses, andapertures, it is preferred that it be made of a polymeric material,whereby it can be formed by means of a molding process for formingshaped articles. Examples of materials suitable for preparing thebacking include, but are not limited to, polyester, polyethyleneterephthalate, and polycarbonate.

The major surface of the backing 114 that contains the recessed portions132 has a plurality of channels 150 formed therein to allow for the flowof a liquid sample. As shown in FIGS. 7 and 8, one end 152 of thechannel 150 is adjacent to the aperture 138 to enable transfer ofbiological fluid from the subject to the channel 150. The other end 154of the channel 150 terminates at a vent opening or a physical end of thechannel or at a flow-terminating interface. The portion of the channel150 between the two ends 152 and 154 can include a surfactant-coatedmesh to aid the wicking of the sample into the reaction site. In otherembodiments, the dimensions of the channel can be selected to allow thesample to be taken into the reaction site by capillary attraction.

Each sector 128 has a channel 150. At the end 152 of the channel 150 isa reaction site 156. The volume of the channel 150 is selected tocontain the amount of sample needed to perform a test. The selection ofthe volume is based on the spacing of the electrodes of the electrodearrangement. The dimensions of the channel 150 are derived from thevolume of liquid sample required. A typical volume for the channel 150ranges from about 0.1 microliter to about 4 microliters, thereby callingfor dimension of from about 0.5 mm×0.2 mm×0.1 mm to about 2 mm×1 mm×0.2mm for a rectangularly-shaped channel.

The layer of adhesive 148 has an aperture 158 into which the biologicalfluid can pass into a channel 160 formed in the layer of adhesive 148.The channel 160 has a first end 160 a and a second end 160 b.

The backing 114 can provide several functions for enhancing the use of alancing device, such as, for example, a motion-terminating element (notshown) for a mechanical lancing device or a support for alight-generating device, e.g., a laser, to prevent contamination oflaser optics. The support can be designated an optical shield and issubstantially similar to the support 48 shown in FIG. 2.

In this embodiment, elimination of the thin, flat plate and the layer ofadhesive joining the thin, flat plate to the backing can lead todecreased manufacturing complexity and cost. The backing can also definethe perimeter of the channel through which the biological fluid flows,which can lead to tighter tolerances in the perimeter of the channel,hence, tighter tolerances in the volume of the channel.

A third embodiment is shown in FIGS. 9-11. In this embodiment, in whichthe biosensors can be packaged in a configuration that is somewhatsimilar to a roll or a cartridge, as in a film cartridge, the article210 comprises a backing 214, which comprises a plurality of segments 228that are arranged in a line. Other configurations for attaching aplurality of segments include, but are not limited to, the following:(a) a fan-fold configuration, in which the segments resemble the foldsof a fan or the pleated bellows of an accordion; (b) a round trackconfiguration, which resembles a roll; (c) an L-shaped configuration, inwhich the segments do not form a closed loop. Each segment 228 isdetachable from the segment 228 or segments 228 adjacent thereto. Eachsegment 228 has sufficient surface area to support a biosensor 230,e.g., a biosensor in the form of a test strip. In each segment 228,there is an aperture 232 adjacent to the test strip 230. The purpose ofthe aperture 232 is to allow passage of a lancing device for forming anopening in the skin and further for allowing biological fluid emergingfrom the opening in the skin to have access to the biosensor 230. On onemajor surface 234 of the backing 214 are a plurality of recesses 236,one recess 236 per segment 228. These recesses 236 have the function ofpositioning and retaining the biosensors 230.

The biosensor 230 in each segment 228 has access to the aperture 232through which biological fluid emerges from the subject or patient. Asshown in FIGS. 9-11, the aperture 232 is rectangular in shape and partof the aperture 232 is allocated to a given segment and part of theaperture 232 is allocated to the adjacent segment. However, the aperture232 can be of a different shape and can be confined within a givensegment. The aperture 232 of each segment 228 has a notch 238 forproviding an area at which the biological sample can easily be drawninto the test strip 230. As in the embodiments shown in FIGS. 1-3 and6-8, the notch 238 breaks the surface tension of the liquid and providesa larger surface area for application of a liquid sample. A layer ofadhesive 240 can be used to adhere the test strip 230 to the backing214.

Each of the recesses 236 has a first end 236 a and a second end 236 band is of sufficient size and appropriate shape to accommodate abiosensor in the form of a test strip 230. The depth of the recess 236is approximately equal to or greater than the thickness of the teststrip 230. The length of the recess 236 is approximately equal to orgreater than the length of the test strip 230. The test strip will bedescribed later.

As stated previously, the article 210 is in the form of a roll orcartridge, as in a film cartridge. The article 210 preferably contains asufficient number of segments 228 for accommodating the desired numberof test strips. The number of segments 228 in the article determines thelength of the article. The overall depth of the backing 214 is notcritical, but should be of sufficient length to ensure structuralintegrity. The depth must not be so great as to require the apparatusinto which it is inserted to be excessively large. Further, the depthmust not be so great that the article cannot be stored in the form of aroll. Typical dimensions of the backing 214 can range and from about 0.5to about 5 mm in thickness. Each segment 228 should be of sufficientwidth to accommodate a single test strip 230. The backing 214 can bemade of the same type of material that can be used to form the backing114.

Each segment 228 has a channel 248 formed therein to allow for the flowof a liquid sample. As shown in FIG. 11, one end 248 a of the channel248 is adjacent to the aperture 232 to enable transfer of biologicalfluid from the subject to the channel 248. The other end 248 b of thechannel 248 terminates at a vent opening or a physical end 248 betweenthe two ends 248 a and 248 b can include a surfactant-coated mesh to aidthe wicking of the sample into the reaction site. In other embodiments,the dimensions of the channel can be selected to allow the sample to betaken into the reaction site by capillary attraction.

At the end 248 a of the channel 248 is a reaction site 250. The volumeof the channel 248 is selected to contain the amount of sample needed toperform a test. The selection of the volume is based on the spacing ofthe electrodes of the electrode arrangement. The dimensions of thechannel 248 are derived from the volume of liquid sample required. Atypical volume for the channel 248 ranges from about 0.1 microliter toabout 4 microliters, thereby calling for dimension of from about 0.5mm×0.2 mm×0.1 mm to about 2 mm×1 mm×0.2 mm for a rectangularly-shapedchannel.

The layer of adhesive 240 has an aperture 252 into which the biologicalfluid can pass into a channel 254 formed in the layer of adhesive 240.The channel 254 has a first end 254 a and a second end 254 b.

In one desirable variation of this embodiment, the segments 228 can berendered more easily detachable from one another by means ofperforations or score lines 256 between the segments 228. Adjacentsegments can be separated by either tearing along a perforation, orscore line, or having a cutting device disconnect a given segment froman adjacent segment. In each segment 228 there can be slot 258 formedtherein for facilitating the advancing of the segments 228 for movingthe notch 238 closer to the sample of biological fluid emerging from theskin and through the aperture 232 so that the biological fluid can bereadily taken up at the sample application site of the test strip 230. Aslot 260 adjacent to the slot 258 can be used for indexing of thesegments 228 in order to transport a used test strip 230 away from thelancing zone.

A fourth embodiment of the article of this invention is shown in FIGS.12-14. In this embodiment, in which the biosensors can be packaged in aconfiguration that is somewhat similar to a roll or a cartridge, as in afilm cartridge, the article 310 comprises a backing 314, which comprisesa plurality of segments 328 that are arranged in a line. Each segment328 is detachable from the segment 328 or segments 328 adjacent thereto.Each segment 328 has sufficient surface area to support a biosensor 330,e.g., a biosensor in the form of a test strip. In each segment 328,there is an aperture 332 adjacent to the test strip 330. The purpose ofthe aperture 332 is to allow passage of a lancing device for forming anopening in the skin and further for allowing biological fluid emergingfrom the opening in the skin to have access to the test strip 330. Onone major surface 334 of the backing 314 are a plurality of recesses336, one recess 336 per segment 328. These recesses 336 have thefunction of positioning and retaining the biosensors 330.

The biosensor 330 in each segment 328 has access to the aperture 332through which biological fluid emerges from the patient. As shown inFIGS. 12-14, the aperture 332 is trapezoidal in shape and part of theaperture 332 is allocated to a given segment and part of the aperture332 is allocated to the adjacent segment. However, the aperture 332 canbe of a different shape and can be confined within a given segment. Theaperture 332 of each segment 328 has a notch 338 for providing an areaat which the biological sample can easily be drawn into the test strip330. As in the embodiments shown in FIGS. 1-3 and 6-11, the notch 338breaks the surface tension of the liquid and provides a larger surfacearea for application of a liquid sample. A layer of adhesive 340 can beused to adhere the test strip 330 to the backing 314.

Each of the recesses 336 has a first end 336 a and a second end 336 band is of sufficient size and appropriate shape to accommodate a teststrip 330. The depth of the recess 336 is approximately equal to orgreater than the thickness of the test strip 330. The length of therecess 336 is approximately equal to or greater than the length of thetest strip 330. The test strip will be described later.

As stated previously, the article 310 is in the form of a roll orcartridge, as in a film cartridge. The article 310 preferably contains asufficient number of segments 328 for accommodating the desired numberof test strips. The number of segments 328 in the article determines thelength of the article. The overall depth of the backing 314 is notcritical, but should be of sufficient length to ensure structuralintegrity. The depth must not be so great as to require the apparatusinto which it is inserted to be excessively large. Further, the depthmust not be so great that the article cannot be stored in the form of aroll. Typical dimensions of the backing 314 can range and from about 0.5to about 5 mm in thickness. Each segment 328 should be of sufficientwidth to accommodate a single test strip 330. The backing 314 can bemade of the same type of material that can be used to form the backing114.

Each segment 328 has a channel 348 formed therein to allow for the flowof a liquid sample. As shown in FIG. 14, one end 348 a of the channel348 is adjacent to the aperture 332 to enable transfer of biologicalfluid from the subject to the channel 348. The other end 348 b of thechannel 348 terminates at a vent opening or a physical end of thechannel or at a flow-terminating interface. The portion of the channel348 between the two ends 348 a and 348 b can include a surfactant-coatedmesh to aid the wicking of the sample info the reaction site. In otherembodiments, the dimensions of the channel can be selected to allow thesample to be taken into the reaction site by capillary attraction.

At the end 348 a of the channel 348 is a reaction site 350. The volumeof the channel 348 is selected to contain the amount of sample needed toperform a test. The selection of the volume is based on the spacing ofthe electrodes of the electrode arrangement. The dimensions of thechannel 348 are derived from the volume of liquid sample required. Atypical volume for the channel 348 ranges from about 0.1 microliter toabout 4 microliters, thereby calling for dimension of from about 0.5mm×0.2 mm×0.1 mm to about 2 mm×1 mm×0.2 mm for a rectangularly-shapedchannel.

The layer of adhesive 340 has an aperture 352 into which the biologicalfluid can pass into a channel 354 formed in the layer of adhesive 340.The channel 354 has a first end 354 a and a second end 354 b.

In one desirable variation of this embodiment, the segments 328 can berendered more easily detachable by means of a rupturable link 356, orflexible connection, between adjacent segments 328. Adjacent segmentscan be separated by breaking the rupturable link, or flexibleconnection, by either tearing along a perforation or having a cuttingdevice disconnect a given segment from an adjacent segment. In eachsegment there can be a slot 358 formed therein for facilitating theadvancing of the segments 328 for moving the notch 338 closer to thesample of biological fluid emerging from the skin and through theaperture 332 so that the biological fluid can be readily taken up at thesample application zone of the test strip 330. A slot 360 adjacent tothe slot 358 can be used for indexing of the segments 328 for in orderto transport a used test strip 330 away from the lancing zone.

In FIG. 13 are shown electrical contact pads 362, which can be formed toincrease the density of material of the electrical contacts and increaseflexibility of the electrical contacts, e.g., with respect toorientation of electrical contacts within the meter. The electricalcontacts 362 can be pre-formed and then placed in slots 364 to eliminatethe need for printing the contacts on the biosensor. Pre-formedelectrical contacts can be used in other embodiments at the discretionof the manufacturer.

A fifth embodiment of the article of this invention is shown in FIGS.15-18. In this embodiment, which is also somewhat similar to a roll or acartridge, as in a film cartridge, the article 410 comprises a backing414, which comprises a plurality of segments 428 that are arranged in aline. Each segment 428 is detachable from the segment 428 or segments428 adjacent thereto. Each segment 428 has sufficient surface area tosupport a biosensor 430, e.g., a biosensor in the form of a test strip.In each segment 428, there is an aperture 432 adjacent to the biosensor430. The purpose of the aperture 432 is to allow passage of a lancingdevice for forming an opening in the skin and further for allowingbiological fluid emerging from the opening in the skin to have access tothe biosensor 430. On one major surface 434 of the backing 414 are aplurality of recesses 436, one recess 436 per segment 428. Theserecesses 436 have the function of positioning and retaining the teststrips 430.

The biosensor 430 in each segment 428 has access to the aperture 432through which biological fluid emerges from the patient. As shown inFIGS. 16-18, the aperture 432 is trapezoidal in shape and part of theaperture 432 is allocated to a given segment and part of the aperture432 is allocated to the adjacent segment. However, the aperture 432 canbe of a different shape and can be confined within a given segment. Theaperture 432 of each segment 428 has a notch 438 for providing an areaat which the biological sample can easily be drawn into the test strip430. As in the embodiments shown in FIGS. 1-3, 6-14, the notch 438breaks the surface tension of the liquid and provides a larger surfacearea for application of a liquid sample. A layer of adhesive 440 can beused to adhere the test strip 430 to the backing 414.

Each of the recesses 436 has a first end 436 a and a second end 436 band is of sufficient size and appropriate shape to accommodate a teststrip 430. The depth of the recess 436 is approximately equal to orgreater than the thickness of the test strip 430. The length of therecess 436 is approximately equal to or greater than the length of thetest strip 430. The test strip will be described later.

As stated previously, the article 410 is in the form of a roll orcartridge, as in a film cartridge. The article 410 preferably contains asufficient number of segments 428 for accommodating the desired numberof test strips. The number of segments 428 in the article determines thelength of the article. The overall depth of the backing 414 is notcritical, but should be of sufficient length to ensure structuralintegrity. The depth must not be so great as to require the apparatusinto which it is inserted to be excessively large. Further, the depthmust not be so great that the article cannot be stored in the form of aroll. Typical dimensions of the backing 414 can range and from about 0.5to about 5 mm in thickness. Each segment 428 should be of sufficientwidth to accommodate a single test strip 430. The backing 414 can bemade of the same type of material that can be used to form the backing114.

Each segment 428 has a channel 448 formed therein to allow for the flowof a liquid sample. As shown in FIG. 17, one end 448 a of the channel448 is adjacent to the aperture 432 to enable transfer of biologicalfluid from the subject to the channel 448. The other end 448 b of thechannel 448 terminates at a vent opening or a physical end of thechannel or at a flow-terminating interface. The portion of the channel448 between the two ends 448 a and 448 b can include a surfactant-coatedmesh to aid the wicking of the sample into the reaction site. In otherembodiments, the dimensions of the channel can be selected to allow thesample to be taken into the reaction site by capillary attraction.

At the end 448 a of the channel 448 is a reaction site 450. The volumeof the channel 448 is selected to contain the amount of sample needed toperform a test. The selection of the volume is based on the spacing ofthe electrodes of the electrode arrangement. The dimensions of thechannel 448 are derived from the volume of liquid sample required. Atypical volume for the channel 448 ranges from about 0.1 microliter toabout 4 microliters, thereby calling for dimension of from about 0.5mm×0.2 mm×0.1 mm to about 2 mm×1 mm×0.2 mm for a rectangularly-shapedchannel.

The layer of adhesive 440 has an aperture 452 into which the biologicalfluid can pass into a channel 454 formed in the layer of adhesive 440.The channel 454 has a first end 454 a and a second end 454 b.

In one desirable variation of this embodiment, the segments 428 can berendered more easily detachable by means of a detachable link 456between adjacent segments 428. The detachable link comprises a pin 458and a holder for the pin 460. The holder 460 receives the pin 458. Thedetachable link can be broken by merely forcing the pin 458 out of theholder 460, thereby separating one segment from the adjacent segment.This type of detachable link may be preferable to the perforations andscore lines and the other type of rupturable link on account ofstrength, flexibility, and the ability to pack more segments into thesame volume of space. In each segment 428, there can be a slot 462formed therein for facilitating the advancing of the segments 428 formoving the notch 438 closer to the sample of biological fluid emergingfrom the skin and through the aperture 432 so that the biological fluidcan be readily taken up at the sample application zone of the test strip430. A slot 464 adjacent to the slot 462 can be used for indexing of thesegments 428 in order to transport a use test strip 430 away from thelancing zone.

A sixth embodiment of the article of this invention is shown in FIG. 19.In this embodiment, a single-use lancet is employed for each biosensor.In this embodiment, which is shown as a variation of the embodimentshown in FIGS. 1-3 or of the embodiment shown in FIGS. 6-8, a pluralityof lancet attachments 470 are fitted into the backing 14, one lancetattachment 470 per sector 30. The lancet attachment 470 includes a head472 and a blade 474. The blades 474 in the lancet attachment 470 can beactivated to form an opening in the skin of a patient by means of apercussion device, an example of which is shown in FIG. 20. Thepercussion device 480 comprises a motor 482, a depth adjustmentmechanism 484, a cam 486, a hammer 488, a return spring 490, and a port492. When a switch (not shown) is activated to begin a test involving abiosensor, the motor 482 is activated and drives the cam 486. Therotational movement of the cam 486 is translated into linear motion ofthe hammer 488. The hammer 488 advances and strikes the head 472 of thelancet attachment 470. The blade 474 of the lancet attachment 470 isthen advanced along its path of travel through the skin of the patientor subject. The blade 474 of the lancet attachment 470 is thenretracted. Retraction of the blade 474 of the lancet attachment 470 canbe carried out in several ways. One simple way involves the use of ahead 472 that is made of a resilient material, e.g., steel, plastic,rubber, and is the shape of a dome. The shape of the dome need not behemispherical (i.e., arc of the dome being 180°). The arc of the domecan be at an angle of less than 180°. The resilient material causes thedome-shaped head 472 to be resiliently biased, so that when the blade474 is in the retracted position, the edge of the dome-shaped head 472is approximately at the same level as the tip of the blade 474. When thehammer 488 strikes the dome-shaped head 472, the resiliency of thematerial of the dome-shaped head causes the dome-shaped head to flattento a sufficient extent to cause the blade 474 to be forced into theskin, thereby forming an opening in the skin. When the return spring 490moves the hammer 488 away from the dome-shaped head 472 of the lancetattachment 470, the resilient biasing of the dome-shaped head 472 causesthe head to reform into the shape of the dome and to revert to itsnormal position, whereby the blade 474 is retracted and again the tip ofthe blade 474 will be approximately at the same level as the edge of thedome-shaped head 472. The sample emerges from the opening formed in theskin by the blade 474 and is transferred directly to the proper positionon the biosensor. The depth adjustment mechanism 484 is set by the userto specify the length of travel of the hammer 488. The port 492 servesas a guide for the hammer 488.

Turning now to a discussion of the biosensors, biosensors of theelectrochemical type can be printed onto a thin, flat plate as in FIGS.1-3 or can be pre-manufactured test strips as in FIGS. 6-18. The choiceof using a printed biosensor or a pre-manufactured test strip is in thediscretion of the manufacturer.

The same, or similar, electrode arrangement can be used for eachembodiment, or a different electrode arrangement can be used for eachembodiment. For ease of manufacture, it is preferred that only oneelectrode arrangement be used in each embodiment.

Referring now to FIGS. 21 and 22, a biosensor 500, which is in the formof a test strip, comprises a base layer 502, conductive tracks 504 a,504 b, and 504 c for electrochemical use, a reaction site 506, aninsulating layer 508 to delineate a specified sensor area 510, a spacerlayer 512 to specify the width and depth of a flow channel 514, a coverlayer 516 to enclose the flow channel 514. The sample is caused to flowin the flow channel 514 by means of capillary attraction. Aflow-terminating interface is designated by the reference numeral 518. Asample application zone is designated by the reference numeral 520. Sucha biosensor is shown in detail in U.S. application Ser. No. 10/266,548,filed Oct. 8, 2002, which is now U.S. Application Publication No.2004-0067166-A1, published Apr. 8, 2004, incorporated herein byreference.

Sensor response is compromised if the sample flows during the analysis;thus, termination of the flow of the sample is extremely desirable. Atleast one opening 522 is formed in the sensor strip 500 in communicationwith the flow channel 514 to bleed air to reduce the pressure thatresists uptake of the sample. This pressure prevents the sample fromtraversing the flow channel 514.

The base layer 502 is preferably made of an inert polymeric material.Representative materials that can be used to form the base layer 502include, but are not limited to, poly(vinyl chloride), polycarbonate,and polyester. The dimensions of the base layer 502 are not critical,but a typical base layer 502 has a length of from about 20 mm to about40 mm, a width of from about 3 mm to about 10 mm, and a thickness offrom about 0.5 mm to about 1 mm.

The conductive tracks 504 a, 504 b, and 504 c are made of anelectrically conductive material. Representative materials that can beused to form the electrically conductive tracks 504 a, 504 b, and 504 cinclude, but are not limited to, carbon, platinum, palladium, gold, anda mixture of silver and silver chloride. The tracks 504 a, 504 b, and504 c determine the positions of electrical contacts 523 a, 523 b, and523 c, respectively, and the electrodes, which will be described later.The third track can be omitted in the absence of a third electrode. Theelectrical contacts are insertable into an appropriate measurementdevice (not shown).

The reaction site 506 comprises an arrangement of electrodes, and,optionally, one or more layers of reagents. The electrode arrangement ofthe sensor strip preferably includes either two or three electrodes. Ina two-electrode system (not shown), a working electrode and dual-purposereference/counter electrode define the electrode arrangement. A thirdelectrode (trigger electrode) can be optionally added to indicate thatthe reaction site 506 is filled. The trigger electrode prevents theassay from beginning until an adequate quantity of sample has filled thereaction site 506. A two-electrode system is described more completelyin U.S. Pat. No. 5,509,410, incorporated herein by reference. Thereference electrode can be positioned so as to act as a triggerelectrode to initiate the assay sequence in the absence of the thirdelectrode.

In a three-electrode system, which is illustrated in FIGS. 21 and 22, aworking electrode 524, a reference electrode 526, and a counterelectrode 528 define the electrode arrangement. The function of theworking electrode 524 is to measure the reaction that takes place in thereaction site 506, e.g., the reaction of glucose with glucose oxidase orglucose dehydrogenase. The function of the reference electrode 526 is tomaintain a desired potential at the working electrode. The function ofthe counter electrode 528 is to provide the necessary current flow atthe working electrode 524. In this system the counter electrode 528 canhave the secondary function of a trigger electrode, that is, preventsthe assay from beginning until an adequate quantity of sample has filledthe reaction site 506.

The reaction that takes place at the working electrode 524 is thereaction that is required to be measured and controlled, e.g., thereaction of glucose with glucose oxidase or with glucose dehydrogenase.The functions of the reference electrode 526 and the counter electrode528 are to ensure that the working electrode 524 actually experiencesthe desired conditions, i.e. the correct potential. The potentialdifference between the working electrode 524 and the reference electrode526 is assumed to be the same as the desired potential at the workingelectrode 524. In an ideal reference electrode, no current passesthrough the reference electrode, and the reference electrode maintains asteady potential; in the case of a dual-purpose reference/counterelectrode, current does pass through the dual-purpose reference/counterelectrode, and thus, the dual-purpose reference/counter electrode doesnot maintain a steady potential. At low currents, the potential shift issmall enough such that the response at the working electrode is notsignificantly affected, and hence the dual-purpose reference/counterelectrode is designated a pseudo-reference electrode. The dual-purposereference/counter electrode still carries out its counter electrodefunction; however, in the case of the dual-purpose reference/counterelectrode, the potential that is applied between the dual-purposereference/counter electrode and the working electrode cannot be alteredto compensate for changes in potential at the working electrode.

The electrodes 524, 526, and 528 are made of an electrically conductivematerial. Representative materials that can be used to form theelectrodes 524, 526, and 528 include, but are not limited to, carbon,platinum, palladium, and gold. The reference electrode 526 canoptionally contain a layer comprising a mixture of silver and silverchloride. The dimensions of the electrodes 524, 526, and 528 are notcritical, but a typical working electrode has an area of from about 0.5mm² to about 5 mm², a typical reference electrode has an area of fromabout 0.2 mm² to about 2 mm², and a typical counter electrode has anarea of from about 0.2 mm² to about 2 mm².

The working electrode 524 comprises a layer of conductive materialcontaining a working area. The working area can include an ink (referredto a working ink), which is deposited on the layer of conductivematerial of the working area. The working ink comprises a reagent systemthat is sensitive to the analyte of interest.

The working area is formed from a working ink that includes a reagentsuitable for the subject test. The reagent may include a mixture of anenzyme (e.g., glucose dehydrogenase or glucose oxidase for a glucoseassay), a redox mediator (such as an organic compound, e.g., aphenanthroline quinone, an organometallic compound, e.g., ferrocene or aferrocene derivative, a coordination complex, e.g., ferricyanide), and aconductive filler material (e.g., carbon) or non-conductive fillermaterial (e.g., silica). Alternatively, instead of an enzyme, theworking area can contain a substrate that is catalytically reactive withan enzyme to be measured. The respective printing inks are applied tothe electrode 524, and, optionally, electrode 526 or electrode 528, orboth, as discrete areas of fixed length. The printing inks can appliedby means of screen-printing. The printing inks can further include apolysaccharide (e.g., a guar gum, an alginate, cellulose or a cellulosicderivative, e.g., hydroxyethyl cellulose), a hydrolyzed gelatin, anenzyme stabilizer (e.g., glutamate or trehalose), a film-forming polymer(e.g., a polyvinyl alcohol), a conductive filler (e.g., carbon) ornon-conductive filler (e.g., silica), a defoaming agent, a buffer, or acombination of the foregoing.

The electrodes cannot be spaced so far apart that the working electrode524, the reference electrode 526, and the counter electrode 528 (or thedual-purpose reference/counter electrode and the working electrode in analternative embodiment) cannot be covered by the sample. It is preferredthat the length of the path to be traversed by the sample (i.e., thesample path) be kept as short as possible in order to minimize thevolume of sample required. The maximum length of the sample path can beas great as the length of the sensor strip. However, the correspondingincrease in resistance of the sample limits the length of the samplepath to a distance that allows the necessary response current to begenerated. The solution resistance is also influenced by the distancefrom the edge of the area of the reference electrode 526 to the edge ofthe working area of the working electrode 524 (or by the distance fromthe dual-purpose reference/counter electrode to the edge of the workingarea of the working electrode in an alternative embodiment). Reducingthe distance between the reference electrode 526 and the workingelectrode 524 (or the dual-purpose reference/counter electrode from theworking electrode in an alternative embodiment) decreases the solutionresistance. Positioning the electrodes in a spaced-apart manner has theadvantage of preventing completion of a circuit (and thus preventingdetection of a response current) before the working electrode has beencompletely covered by sample.

The elongated portions of the conductive tracks 504 a, 504 b, and 504 ccan optionally be overlaid with a track of conductive material,preferably made of a mixture comprising silver particles and silverchloride particles. This optional overlying track results in lowerresistance, and consequently, higher conductivity. Optionally, a layerof a hydrophobic electrically insulating material 508 further overliesthe tracks 504 a, 504 b, and 504 c. The layer of hydrophobicelectrically insulating material 508 does not cover the positions of thereference electrode 526, the working electrode 524, the counterelectrode 528, and the electrical contacts. In the embodiment employingthe dual-purpose reference/counter electrode (in an alternativeembodiment), the layer of hydrophobic electrically insulating materialdoes not cover the positions of the dual-purpose reference/counterelectrode, the working electrode, any third electrode, and theelectrical contacts. This layer of hydrophobic electrically insulatingmaterial 508 serves to prevent short circuits. Because this insulatingmaterial is hydrophobic, it can cause the sample to be restricted to theexposed electrodes. A preferred insulating material is commerciallyavailable as “POLYPLAST” (Sericol Ltd., Broadstairs, Kent, UK).

The reaction site 506 is not limited to reaction sites appropriate toelectrochemical sensors. In a photometric sensor (not shown), thereaction site can comprise a reagent system that changes its opticalproperties (e.g., absorbance, reflectance) as a function of the presenceof or the amount of an analyte. A photometric sensor is similar to thesensor shown in FIGS. 1, 2, 3, and 4, with the exception that theelectrodes and tracks are removed, and, at the reaction site, at least aportion of the flow channel comprises a light transmissive material sothat a source of light can transmit light through the light transmissivematerial to provide a signal related to the presence or the amount of ananalyte in the sample, e.g., absorbance or reflectance. This opticalsignal can be detected and measured. In conjunction with the lighttransmissive material, at least one reagent for a specified assay can belocated at or transported to the reaction site. In still another type ofsensor (not shown), the reaction site can comprise an ion-selectiveelectrode.

The spacer layer 512 comprises a material of substantially uniformthickness that can bond to the first major surface 530 of the base layer502 and to the first major surface 532 of the cover layer 516.

In certain embodiments, the base layer 502 is not required. For example,in the embodiments shown in FIGS. 1-3, no base layer is required—thethin, flat plate 12 itself performs the functions of the base layer 502.

Capillary attraction is very desirable as the fluid transfer mechanismfor the biological fluid. The analyte meter can be designed to use thesame indexing mechanism to move the entrance of a capillary channel of agiven test strip to the lancing site after the lancing step to collect asample of biological fluid, e.g., blood.

One of the key benefits of this invention is the multiple-biosensorarticle for an apparatus that integrates lancing the skin of a patient,collecting biological fluid from the patient, e.g., blood, and measuringthe concentration of an analyte in the biological fluid of the patient.The invention eliminates the manual handling of individual test strips,the manual lancing of the skin of the patient, and the manual collectingof biological fluid from the patient.

Because there is no need to handle each test strip individually, thephysical size of each test strip can be greatly reduced. As aconsequence, the number of biosensors that can be placed in a given areaof a multiple-biosensor article can be increased.

The multiple-biosensor article can be made in a number of ways, some ofwhich will be described. In the embodiment shown in FIGS. 1-3, aplurality of biosensors are printed on a thin, flat, circular plate suchthat the electrically conductive tracks are aligned along the radius ofthe plate. The electrodes are located near the periphery of the thin,flat plate and the electrical contacts are located toward the center ofthe thin, flat, circular plate. The plate has apertures adjacent to theelectrodes in order to allow the skin to be pierced by the lancingdevice that moves perpendicular to and through the major surfaces of theplate. The same effect can be achieved by a cutting an area of the platethat is adjacent to the electrodes in order to provide unrestricted areafor the skin to be pierced.

The thin, flat plate 12 is then attached to the backing 14. Attachmentcan be achieved, for example, by using an adhesive layer or by aninterlocking mechanism, e.g., a press-fit ring. As shown in FIGS. 1-3,the backing 14 has apertures 38 in the recessed portions 32 that will bealigned with the apertures 20 on the plate 12. The plate 12, the layerof adhesive 50, and the backing 14 cooperate to form a plurality ofcapillary chambers. Each of these capillary chambers will be associatedwith an electrode arrangement, and the combination will be sufficientfor creating a biosensor suitable for performing an assay.

The backing 14 can be formed from a polymeric material by means of aninjection molding technique. Injection molding is a common techniqueused to create plastic components. The backing 14 can be molded insingle form or be molded with a carrier to assist in manufacturing. Acarrier would allow for the parts to be stored and transported on a reelfor subsequent feeding into a continuous assembly step at a later time.It is preferred, but not required, that the backing 14 have features toenable alignment of the plate 12 with the backing 14.

As stated previously, the electrode arrangements can be prepared byscreen printing inks onto a major surface of the plate 12.

The stages of ink deposition and their variations are well known tothose of ordinary skill in the art. Descriptions of printing can befound, for example, in U.S. Pat. No. 5,509,410, incorporated herein byreference.

A layer of mesh and a layer of tape would not be required. These twocomponents would be replaced by the backing (i.e., at least one surfaceof the backing would duplicate the function of the mesh and tape). Asuitable material for adhering the backing to the plate is adouble-stick adhesive tape. Some benefits of the use of tape would beease of handling and control of the depth and perimeter of the channel.Once the plate and the backing are combined, the product issubstantially ready for use.

In the embodiment shown in FIGS. 1-3, the backing can be prepared byinjection molding. In the embodiment shown in FIGS. 6-8, the backing canbe prepared by injection molding and the biosensors can be inserted intothe recesses by machinery. In the embodiments shown in FIGS. 9-14, thebacking can be prepared by injection molding and the biosensors can beinserted into the recesses by machinery. In the embodiment shown inFIGS. 15-18, the segments can be prepared by injection molding,assembled to form the backing, and the biosensors can be inserted intothe recesses by machinery. Biosensors that are not printed onto theplate 12 or the backing 14 can be manufactured in a conventional mannerand inserted into the appropriate recesses of the article by machinery.

In each embodiment described herein, there is an opening in or near eachsector or each segment through which the lancing device can pass on theway to lancing the skin. The lancing device is preferably orientedperpendicular to the surface of the plate 12 or to the surface of thesegment of a roll. The multiple-biosensor article can be used with alltypes of mechanical and laser lancing devices. The various test stripsare used in sequence, not simultaneously.

The multiple-biosensor article should be of a size to fit within ananalyte meter. As shown in FIGS. 4 and 5, an analyte meter 600 comprisesa chamber 602 for accommodating the article 604 of this invention. Thechamber 602 contains the mechanism(s) (not shown) required to allowpositioning of the article for testing, pausing, and for removal aftertesting. This positioning or indexing function can be carried outautomatically, semi-automatically, or manually.

The multiple-biosensor article can be loaded into the analyte meter 600by inserting the article 604 into a slot located on or in the analytemeter, which slot communicates with the aforementioned chamber (notshown). The slot provides a path for the article to follow so that itcan be moved into a stand-by or a test position. Another method ofloading the article into analyte meter 600 would involve opening a dooror cover 606 on or in the analyte meter 600 and inserting the article604 into the area provided. In the embodiment shown in FIGS. 4 and 5,the article is placed on a rotatable platform 608, which is designed torotate in order to position a given biosensor in the appropriate areafor the lancing of the skin of a patient and the collection ofbiological fluid from the opening in the skin of the patient.

Once loaded in the analyte meter 600, the multiple-biosensor article 604can be advanced or indexed or both by either rotating or translating thearticle automatically, semi-automatically, or manually. Advancing orindexing or both can be carried out by such mechanisms as motor(s),gear(s), pulley(s), belt(s), solenoid(s), nano-muscle(s), and the like(not shown).

After the lancing step, the multiple-biosensor article can be indexedslightly to cover the lancing site with the sample pick-up area of abiosensor to fill the reaction site of the biosensor.

After a test is completed, the flat, circular embodiments of thisinvention (e.g., FIGS. 1-3) may be advanced or indexed by rotation,automatically, semi-automatically, or manually, toward a storage areawithin the analyte meter. Used biosensors in the flat, circularembodiment may have to remain within the analyte meter until all of thebiosensors are consumed. After the biosensors of the flat, circularembodiments have been used, they can be removed simply by lifting thearticle 604 off the rotatable platform 608. For the linear embodiments(e.g., FIGS. 6-18), only the segment used for the most recent test needbe advanced or translated to an area that would allow for its removaleither automatically or manually.

In order to use the device of this invention in an effective manner, theanalyte meter has a drive mechanism to advance a given biosensor when itis required for a test. In the embodiments where the multiple-biosensorarticle is in the shape of a disk, the drive mechanism should be capableof rotating the disk about its axis. Mechanisms for rotating disk-shapedobjects are well-known in the art. Representative examples of mechanismscapable of rotating disk-shaped objects include, but are not limited to,motors, gears, solenoids, nano-muscles, belts, linkages, pulleys, etc.In the embodiments where the multiple-biosensor article is in theconfiguration of a roll (or fan-fold, or round track, or L-shape), thedrive mechanism should be capable of advancing the segments linearly tothe area where the biological sample is to be collected. Representativeexamples of mechanisms capable of advancing segments of a roll linearlyinclude, but are not limited to, motors, gears, solenoids, nano-muscles,belts, linkages, pulleys, etc.

The article of this invention can include calibration to minimize thenumber of steps required to perform a test for determining theconcentration of an analyte. Calibration techniques suitable for useherein include, but are not limited to, a memory device (integratedcircuit), resistive, or mechanical feature.

Various types of indicators for Identifying particular assays forparticular analytes (ketone, glucose) can be employed with the articleof this invention.

The adhesive suitable for use herein can be of the two-sided tapevariety. Alternatively, in place of a two-sided tape, a liquid adhesivecan be used. Such a liquid adhesive could be applied via screen printingor pad printing.

Various modifications and alterations of this invention will becomeapparent to those skilled in the art without departing from the scopeand spirit of this invention, and it should be understood that thisinvention is not to be unduly limited to the illustrative embodimentsset forth herein.

It should also be noted that various modifications and alterations shownin certain embodiments of the invention, illustrated herein, can be usedin other embodiments. Such modifications and alterations include, butare not limited to, the means for separating adjacent segments of a rollor a cartridge, or the like, the means for applying the electricalcontacts of the biosensors, and the types of biosensors and electrodearrangements for a given embodiment, e.g., the use of biosensors havingelectrode arrangements that are printed directly onto a sector of athin, flat plate or a segment of a roll or a cartridge, or the like, theuse of pre-formed test strips that are subsequently applied to a recessin a segment of a roll or a recess in a backing.

1. An article for providing a plurality of test strips, said articlecomprising: (a) a thin, flat plate comprising 1) a sample receiving sideand 2) a backing-facing side that is opposite the sample receiving side;wherein said thin, flat plate has a plurality of sectors, each of saidsectors comprising: an electrode arrangement applied thereto on thebacking-facing side, and a first aperture for receiving a sample,wherein the electrode arrangement is adjacent the first aperture; (b) abacking comprising 1) a lancet-receiving side and 2) a plate-facing sidethat is opposite the lancet-receiving side, wherein the plate-facingside faces the backing-facing side of the thin, flat plate; wherein thebacking has a plurality of sectors, each of said sectors having arecessed portion on the lancet-receiving side of the backing, therecessed portion comprising a wall portion and a base portion, andwherein the base portion includes a second aperture therethrough,wherein the wall portion is arranged and configured to guide a lancingdevice through the recessed portion and second aperture in from thelancet-receiving side and out the plate-facing side of the backing;wherein the plate-facing side of the backing includes a flow channelextending from the second aperture along a major surface of theplate-facing side of the backing, and wherein the flow channel is inregister with the second aperture and said electrode arrangement;wherein said major surface of said plate-facing side of the backing isin facing orientation to the backing-facing side of said thin, flatplate such that the flow channel is on the plate-facing side of thebacking and in facing arrangement with the electrode arrangement;wherein said first aperture is in facing arrangement with said secondaperture, said first aperture is in register with said second aperturein said base portion of said backing, wherein the electrode arrangementis disposed on the thin, flat plate adjacent to the first and secondapertures; wherein said lancing device passes first through the recessedportion of the lancet-receiving side of said backing and then throughsaid second and first apertures out to the sample receiving side of thethin, flat plate.
 2. The article of claim 1, wherein each of said firstapertures in said thin, flat plate has a notch located on the peripherythereof.
 3. The article of claim 1, wherein one major surface of saidthin, flat plate is adhered to said major surface of said backingcomprising said second aperture.
 4. The article of claim 3, wherein alayer of adhesive adheres said one major surface of said thin, flatplate to said major surface of said backing, said layer of adhesivecomprising a plurality of channels for the transport of biological fluidfrom the skin of a patient to said electrode arrangements.
 5. Thearticle of claim 1, wherein said thin, flat plate has a central openingand said backing has a central opening.
 6. The article of claim 1,wherein the major surfaces of said thin, flat plate and said backing arecircular in shape.
 7. The article of claim 6, wherein said article isadvanced by rotating said article.
 8. The article of claim 1, furtherincluding a plurality of alignment posts for ensuring that said firstaperture in said thin, flat plate is in register with said secondaperture in said recessed portion in said backing.
 9. The article ofclaim 1, wherein said backing is attached to said thin, flat plate bymeans of press-fitting.
 10. The article of claim 1, wherein said backingis attached to said thin, flat plate by means of a weld.
 11. The articleof claim 1, wherein each electrode arrangement comprises a workingelectrode and a second electrode.
 12. The article of claim 11, whereinthe second electrode is a counter electrode and said electrodearrangement further comprises a reference electrode.
 13. The article ofclaim 12, wherein said counter electrode functions as a triggerelectrode.
 14. The article of claim 1, wherein said first and secondapertures are circular in shape.
 15. The article of claim 1, whereinsaid thin, flat plate and said backing are made of polymeric material.16. The article of claim 1, wherein said flow channel includes a mesh.17. The article of claim 1, wherein said flow channel has a volumeranging from 0.1 to 4 μL.
 18. The article of claim 1, further comprisinga plurality of lancets.
 19. The article of claim 18, wherein saidplurality of lancets comprises a head and a blade.
 20. The article ofclaim 1, wherein said electrode arrangement comprises a workingelectrode and a dual-purpose reference/counter electrode.
 21. Thearticle of claim 1, wherein said article is used for a glucose assay.